Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Satyabrata Pany, Anamitra Ghosh, Youngki You, Nga Nguyen, Joydip Das
BackgroundResveratrol (1) is a naturally occurring polyphenol that has been implicated in neuroprotection. One of resveratrol's several biological targets is Ca2+-sensitive protein kinase C alpha (PKCα). Resveratrol inhibits PKCα by binding to its activator-binding C1 domain. Munc13–1 is a C1 domain-containing Ca2+-sensitive SNARE complex protein essential for vesicle priming and neurotransmitter release.MethodsTo test if resveratrol could also bind and inhibit Munc13–1, we studied the interaction of resveratrol and its derivatives, (E)-1,3-dimethoxy-5-(4-methoxystyryl)benzene, (E)-5,5′-(ethene-1,2-diyl)bis(benzene-1,2,3-triol), (E)-1,2-bis(3,4,5-trimethoxyphenyl)ethane, and (E)-5-(4-(hexadecyloxy)-3,5-dihydroxystyryl)benzene-1,2,3-triol with Munc13–1 by studying its membrane translocation from cytosol to plasma membrane in HT22 cells and primary hippocampal neurons.ResultsResveratrol, but not the derivatives inhibited phorbol ester-induced Munc13–1 translocation from cytosol to membrane in HT22 cells and primary hippocampal neurons, as evidenced by immunoblot analysis and confocal microscopy. Resveratrol did not show any effect on Munc13–1H567K, a mutant which is not sensitive to phorbol ester. Binding studies with Munc13–1 C1 indicated that resveratrol competes with phorbol ester for the binding site. Molecular docking and dynamics studies suggested that hydroxyl groups of resveratrol interact with phorbol-ester binding residues in the binding pocket.Conclusions and significance.This study characterizes Munc13–1 as a target of resveratrol and highlights the importance of dietary polyphenol in the management of neurodegenerative diseases.
Graphical abstract
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2uaA1Mv
via IFTTT
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου